Identification of archaeal proteins that affect the exosome function in vitro

Background  

The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors.     

Silver(I)‐Catalyzed Enantioselective [3+2]‐Cycloaddition Reaction of α‐Silylimines: A Facile Route to Quaternary‐Carbon‐Rich Scaffolds

A silver‐catalyzed highly enantioselective 1,3‐dipolar cycloaddition reaction of α‐silylimines with pyrone‐based trisubstituted olefins was developed affording bi‐ and tricyclic α‐quaternary‐carbon‐rich pyrano‐pyrrolidines in excellent yields. The tricyclic benzopyrone adducts thus obtained were efficiently transformed into highly complex tetracyclic scaffolds supporting four consecutive stereogenic centers with three quaternary carbons.     

Modulation of humoral immune response to oral BCG vaccination by Mycobacterium bovis BCG Moreau Rio de Janeiro (RDJ) in healthy adults

We hypothesize that the energy strategy of a cell is a key factor for determining how, or if, the immune system interacts with that cell. Cells have a limited number of metabolic states, in part, depending on the type of fuels the cell consumes. Cellular fuels include glucose (carbohydrates), lipids (fats), and proteins. We propose that the cell's ability to switch to, and efficiently use, fat for fuel confers immune privilege. Additionally, because uncoupling proteins are involved in the fat burning process and reportedly in protection from free radicals, we hypothesize that uncoupling proteins play an important role in immune privilege. Thus, changes in metabolism (caused by oxidative stresses, fuel availability, age, hormones, radiation, or drugs) will dictate and initiate changes in immune recognition and in the nature of the immune response. This has profound implications for controlling the symptoms of autoimmune diseases, for preventing graft rejection, and for targeting tumor cells for destruction.     

Anti-Inflammatory and Anti-Rheumatic Potential of Selective Plant Compounds by Targeting TLR-4/AP-1 Signaling: A Comprehensive Molecular Docking and Simulation Approaches

Plants are an important source of drug development and numerous plant derived molecules have been used in clinical practice for the ailment of various diseases. The Toll-like receptor-4 (TLR-4) signaling pathway plays a crucial role in inflammation including rheumatoid arthritis. The TLR-4 binds with pro-inflammatory ligands such as lipopolysaccharide (LPS) to induce the downstream signaling mechanism such as nuclear factor κappa B (NF-κB) and mitogen activated protein kinases (MAPKs). This signaling activation leads to the onset of various diseases including inflammation. In the present study, 22 natural compounds were studied against TLR-4/AP-1 signaling, which is implicated in the inflammatory process using a computational approach. These compounds belong to various classes such as methylxanthine, sesquiterpene lactone, alkaloid, flavone glycosides, lignan, phenolic acid, etc. The compounds exhibited different binding affinities with the TLR-4, JNK, NF-κB, and AP-1 protein due to the formation of multiple hydrophilic and hydrophobic interactions. With TLR-4, rutin had the highest binding energy (−10.4 kcal/mol), poncirin had the highest binding energy (−9.4 kcal/mol) with NF-κB and JNK (−9.5 kcal/mol), respectively, and icariin had the highest binding affinity (−9.1 kcal/mol) with the AP-1 protein. The root means square deviation (RMSD), root mean square fraction (RMSF), and radius of gyration (RoG) for 150 ns were calculated using molecular dynamic simulation (MD simulation) based on rutin’s greatest binding energy with TLR-4. The RMSD, RMSF, and RoG were all within acceptable limits in the MD simulation, and the complex remained stable for 150 ns. Furthermore, these compounds were assessed for the potential toxic effect on various organs such as the liver, heart, genotoxicity, and oral maximum toxic dose. Moreover, the blood–brain barrier permeability and intestinal absorption were also predicted using SwissADME software (Lausanne, Switzerland). These compounds exhibited promising physico-chemical as well as drug-likeness properties. Consequently, these selected compounds portray promising anti-inflammatory and drug-likeness properties.     

Formal synthesis of antiplatelet drug, beraprost

The first stereocontrolled and enantiospecific formal synthesis of antiplatelet drug beraprost has been achieved from readily available 1-tetralone.     

Superacid‐Promoted Cyclodehydration Leading to the Imidazo[2,1‐a]isoquinoline Ring System

A series of heterocycle‐substituted acetophenones were prepared and reacted with the Brønsted superacid CF₃SO₃H (triflic acid=trifluoromethanesulfonic acid). Cyclodehydration provided aryl‐substituted imidazo[2,1‐a]isoquinolines and related products (28–85%, seven examples). A mechanism is proposed involving dicationic intermediates.     

The effect of data scaling on dual prices and sensitivity analysis in linear programs

In many practical situations scaling the data is necessary to solve linear programs. This note explores the relationships in translating the sensitivity analysis between the original and the scaled problems.     

Charge delocalization and enhanced acidity in tricationic superelectrophiles

This Article presents the results from studies related to the chemistry of tricationic superelectrophiles. A series of triaryl methanols were ionized in Br?nsted superacids, and the corresponding tricationic intermediates were formed. The trications are found to participate in two types of reactions; both are characteristic of highly charged organic cations. One set of reactions occurs through charge migration. A second set of reactions occurs through deprotonation of an unusually acidic site on the tricationic species. One of the tricationic intermediates has been directly observed by low temperature NMR spectroscopy. These highly charged ions and their reactions have also been studied using density functional theory calculations. As a result of charge migration, electron density at a carbocation site is found to increase with progression from monocationic to pentacationic structures.